HISTAMINE RELEASE FROM RAT PERITONEAL MAST CELLS: INHIBITION BY COLCHICINE AND POTENTIATION BY DEUTERIUM OXIDE

¹ Departments of Pharmacology and Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

Colchicine and other compounds known to alter the organization of the mitotic spindle were examined for their effects on histamine release from rat peritoneal mast cells. Pretreatment of the cells with colchicine in vitro decreased histamine release induced by either compound 48/80, polymyxin B or reserpine but not that induced by n-decylamine. The degree of inhibition of release by 48/80 depended on both the time of pretreatment and the concentration of colchicine used. Inhibition, once established, remained unchanged for at least 2 hr after removal of colchicine from the medium. Vinblastine, demecolcine and griseofulvin also inhibited histamine release by 48/80. Replacement of 35% of the H₂O in the medium by D₂O resulted in potentiation of histamine release by either 48/80, polymyxin B or reserpine. D₂O, itself, at higher concentrations (40-90%) caused histamine release. This effect was inhibited by colchicine. It is suggested that colchicine, demecolcine, vinblastine, griseofulvin and D₂O all act by aJtering the degree of organization of cytoplasmic structural elements (possibly microtubules) and that these elements might be involved in mast cell degranulation.

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